Breast Cancer Screening in High-Risk Women: Is MRI Alone Enough?

Breast magnetic resonance imaging (MRI) is considered the most sensitive imaging modality for the early detection of breast cancer. The American Cancer Society guidelines and the National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology recommend annual breast MRI screening for women at high risk for breast cancer, which includes BRCA mutation carriers and their untested first-degree relatives; women with Li-Fraumeni syndrome and other high-risk predisposition syndromes; women with a history of thoracic radiation therapy between age 10 and 30 years; and women with 20% or greater lifetime risk of breast cancer based on risk assessment models. Annual MRI screening should start at age 25–30 years and annual mammography screening is also recommended, starting preferably at age 30 years (1,2).

As the effectiveness of mammography screening in high-risk women has been questioned, there remains some uncertainty about its indication for these patients. Of particular concern is the risk of radiation-induced breast cancer, especially in young women and in BRCA1 and BRCA2 (BRCA1/2) carriers (3).

In this issue of the Journal, Chiarelli et al. (4) demonstrated a statistically significant increase in sensitivity for MRI plus mammography screening, rather than when the modalities were used alone for women age 40 to 49 years; the sensitivity for MRI plus mammography was even higher among women age 50 to 69 years. However, Chiarelli et al. (4) found that the benefit of adding mammography to MRI was particularly small among mutation carriers age 30 to 39 years, particularly for BRCA1/2 carriers; this can be attributed to the higher breast density and lower sensitivity of mammography in this age group (5). The findings in Chiarelli et al. (4) are in line with other studies (6, 7) that have also found that the two modalities combined did not statistically significantly improve sensitivity in BRCA1 carriers younger than age 40 years compared with MRI alone, suggesting that mammography screening should be reconsidered in this cohort. A concern is that not performing mammography in these patients could potentially decrease the detection of ductal carcinoma in situ (DCIS); however, the sensitivity of breast MRI for high-grade DCIS is excellent, whereas mammography preferentially depicts lower-grade lesions (8). Chiarelli et al. (4) found that the majority of DCIS was detected by MRI only.

It is known that tumors in mutation carriers grow faster than those in average-risk women at the same age (9). Guindalini et al. (7) performed a prospective study with MRI screening every 6 months and found that MRI screening alone had a higher specificity rate and similar sensitivity to MRI plus annual mammography in mutation carriers, especially in BRCA1 carriers. In this intensive surveillance study, they also demonstrated that there were no patients with lymph node metastasis at the time of diagnosis and no interval invasive cancers. Similarly, Chiarelli et al. (4) did not find any interval cancers in mutation carriers age 30 to 39 years and concluded that annual MRI may be enough in this subgroup; however, it must be noted that most patients in their study had few screening rounds. The disadvantage of biannual MRI is the higher cost, which can be alleviated with abbreviated MRI protocols, which have high diagnostic accuracy (10).

In Chiarelli et al. (4), contrary to the findings in younger women, the addition of mammography to MRI in older women resulted in increased sensitivity, particularly among mutation carriers. This is in line with Phi et al. (11), who also demonstrated that BRCA1/2 carriers age 60 to 74 years benefit from MRI plus mammography screening compared with mammography alone, especially in BRCA2 carriers with dense breasts, who tend to develop breast cancer at an older age compared with BRCA1 carriers. For high-risk patients, with the existing mammography screening recommendations, digital breast tomosynthesis and synthetic mammography images should be preferred over digital mammography because they exhibit higher rates of screen-detected breast cancer and lower false-positive rates (12).

Although mammography screening has been considered the mainstay of breast cancer screening, it has its limitations, especially for high-risk women. MRI, on the other hand, poses no risk of radiation-induced cancer and exhibits high sensitivity, and the potential risks from the application of gadolinium-containing contrast media are minimal. Current evidence supports the use of MRI as an effective breast cancer surveillance tool, especially in high-risk populations, given the aggressive behavior and natural history of mutation-associated breast cancers (13,14). Recent advances in breast MRI, especially abbreviated protocols, support this method alone as an excellent alternative for screening high-risk women younger than age 40 years. On the other hand, mammography can bring additional value for screening high-risk women older than age 40 years, especially age 50 to 69 years, and should be considered as being associated with MRI. Further studies should be performed to ensure the best screening strategy for this population.

Funding

This work was partially supported by the National Institutes of Health–National Cancer Institute Cancer Center Support Grant (P30 CA008748) and the Breast Cancer Research Foundation.

Notes

The funder had no role in the writing of this editorial or the decision to submit it for publication. The authors have no conflicts of interest to disclose.